Identification and Validation of Immune-Related Gene Signature for Predicting Lymph Node Metastasis and Prognosis in Lung Adenocarcinoma

Frontiers in Molecular Biosciences, Journal Year: 2021, Volume and Issue: 8

Published: May 24, 2021

Lung cancer is a serious malignancy, and lung adenocarcinoma (LUAD) the most common pathological subtype. Immune-related factors play an important role in lymph node metastasis. In this study, we obtained gene expression profile data for LUAD normal tissues from TCGA database analyzed their immune-related genes (IRGs), observed that 459 IRGs were differentially expressed. Further analysis of correlation between expressed metastasis revealed 18 metastasis-associated IRGs. addition, mutations status, function pathway enrichment these IRGs, regulatory networks established through TF genes. We then identified eight (IKBKB, LTBR, MIF, PPARD, PPIA, PSME3, S100A6, SEMA4B) as best predictors by LASSO Logistic used to construct model predict patients with (AUC 0.75; 95% CI: 0.7064–0.7978), survival showed risk score independently affected patient survival. validated predictive effect scores on using GEO validation cohort results good agreement. was highly correlated infiltration immune cells (mast activated, macrophages M2, M0 B naïve), stromal scores, checkpoint (LTBR, CD40LG, EDA2R, TNFRSF19). key associated constructed reliable model, which may provide valuable biomarkers further reveal mechanism its occurrence.

Language: Английский

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Osteosarcoma neutrophil extracellular trap network-associated gene recurrence and metastasis model

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(2)

Published: Jan. 29, 2024

Abstract Osteosarcoma (OS) is the most common malignancy in children and adolescents has a high probability of recurrence metastasis. A growing number studies have shown that neutrophil extracellular traps (NETs) are strongly associated with cancer metastasis, but osteosarcoma, genes NETs promote osteosarcoma metastasis remain to be explored. We systematically investigated gene expression patterns OS samples from GEO database. molecular typing was evaluated based on profiles, association between subtypes immune microenvironment metastatic features were Ultimately, we constructed signature model column line graph prediction screened possible potential drugs for osteosarcoma. established two different NETs, which showed significant differences status, time, tumor microenvironment, biological effects. also NETs-related signature(NRGMS) assess pattern patients predict patients. TOMM40 FH Overall, this study constructs predictive genes, expected provide new insights into

Language: Английский

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Osteosarcoma in a ceRNET perspective

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: June 5, 2024

Abstract Osteosarcoma (OS) is the most prevalent and fatal type of bone tumor. It characterized by great heterogeneity genomic aberrations, mutated genes, cell types contribution, making therapy patients management particularly challenging. A unifying picture molecular mechanisms underlying disease could help to transform those challenges into opportunities. This review deeply explores occurrence in OS large-scale RNA regulatory networks, denominated “competing endogenous network” (ceRNET), wherein different biotypes, such as long non-coding RNAs, circular RNAs mRNAs can functionally interact each other competitively binding shared microRNAs. Here, we discuss how unbalancing any network component derail entire circuit, driving onset progression impacting on proliferation, migration, invasion, tumor growth metastasis, even chemotherapeutic resistance, distilled from many studies. Intriguingly, aberrant expression networks components cells be triggered also surroundings, through cytokines vesicles, with their bioactive cargo proteins highlighting relevance microenvironment. comprehensive pave way for development innovative RNA-targeted RNA-based therapies new diagnostic tools, perspective precision oncology.

Language: Английский

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YY1-modulated long non-coding RNA SNHG12 promotes gastric cancer metastasis by activating the miR-218-5p/YWHAZ axis

International Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 17(7), P. 1629 - 1643

Published: Jan. 1, 2021

Long non-coding RNA (lncRNA) small nucleolar host gene 12 (SNHG12) plays important roles in the pathogenesis and progression of cancers.However, role SNHG12 metastasis gastric cancer (GC) has not yet been thoroughly investigated.In present study, we demonstrated that was upregulated GC tissues cell lines.In addition, expression level samples significantly related to tumor invasion depth, TNM stage lymph node associated with disease-free survival (DFS) overall (OS) patients.In vivo vitro assays indicated promotes epithelial-mesenchymal transition (EMT).Bioinformatics mechanistic analyses revealed can directly target miR-218-5p regulate YWHAZ mRNA, forming an SNHG12/miR-218-5p/YWHAZ axis decreasing ubiquitination β-catenin.In stabilizes CTNNB1 mRNA by binding HuR, thus activating β-catenin signaling pathway.Further analysis also transcription factor YY1 negatively modulates transcription.In conclusion, is a potential prognostic marker therapeutic for GC.Negatively modulated YY1, EMT regulating miR-218-5p/YWHAZ stabilizing via activation pathway.

Language: Английский

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Comprehensive analysis of a glycolysis and cholesterol synthesis-related genes signature for predicting prognosis and immune landscape in osteosarcoma

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 23, 2022

Background Glycolysis and cholesterol synthesis are crucial in cancer metabolic reprogramming. The aim of this study was to identify a glycolysis synthesis-related genes (GCSRGs) signature for effective prognostic assessments osteosarcoma patients. Methods Gene expression data clinical information were obtained from GSE21257 TARGET-OS datasets. Consistent clustering method used the GCSRGs-related subtypes. Univariate Cox regression LASSO analyses construct GCSRGs signature. ssGSEA analyze differences immune cells infiltration. pRRophetic R package utilized assess drug sensitivity different groups. Western blotting, cell viability assay, scratch assay Transwell perform cytological validation. Results Through bioinformatics analysis, patients diagnosed with classified into one 4 subtypes (quiescent, glycolysis, cholesterol, mixed subtypes), which differed significantly terms prognosis tumor microenvironment. Weighted gene co-expression network analysis revealed that modules strongly correlated midnight blue yellow modules, respectively. Both univariate conducted on screened module 5 (RPS28, MCAM, EN1, TRAM2, VEGFA) constituting an predictor, independent characteristics, as verified further via Kaplan-Meier ROC curve multivariate analysis. Additionally, had strong correlation sensitivity, checkpoints In experiments, we selected TRAM2 representative validate validity signature, found promoted progression cells. Finally, at pan-cancer level, been overall survival, free disease specific mutational burden, microsatellite instability, Conclusion Therefore, constructed efficiently predicted patient guided therapy.

Language: Английский

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Multi-Omics Immune Interaction Networks in Lung Cancer Tumorigenesis, Proliferation, and Survival

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 14978 - 14978

Published: Nov. 29, 2022

There are currently no effective biomarkers for prognosis and optimal treatment selection to improve non-small cell lung cancer (NSCLC) survival outcomes. This study further validated a seven-gene panel diagnosis of NSCLC using RNA sequencing proteomic profiles patient tumors. Within the panel, ZNF71 expression combined with dendritic activities defined subgroups (n = 966) distinct outcomes (p 0.04, Kaplan-Meier analysis). was significantly associated natural killer cells 0.014) T 0.003) in tumors 1016) Chi-squared tests. Overexpression resulted decreased multiple components intracellular intrinsic innate immune systems, including dsRNA dsDNA sensors. Multi-omics networks systems were computed as relevant tumorigenesis, proliferation, clinical information in-vitro CRISPR-Cas9/RNAi screening data. From these networks, pan-sensitive pan-resistant genes 21 NCCN-recommended drugs treating selected. Based on gene associations CRISPR-Cas9, RNAi, drug data, MEK1/2 inhibitors PD-198306 U-0126, VEGFR inhibitor ZM-306416, IGF-1R PQ-401 discovered potential targeted therapy that may also induce an response NSCLC.

Language: Английский

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THE POTENTIAL EFFECT OF APORPHINE ALKALOIDS FROM NELUMBO NUCIFERA GAERTN. AS ANTI-BREAST CANCER BASED ON NETWORK PHARMACOLOGY AND MOLECULAR DOCKING

International Journal of Applied Pharmaceutics, Journal Year: 2024, Volume and Issue: unknown, P. 280 - 287

Published: Jan. 7, 2024

Objective: To demonstrate the efficacy and benefits of aporphine alkaloids from Nelumbo nucifera Gaertn. as anti-breast cancer agents. Methods: In this study, a combination network pharmacology molecular docking was used to investigate pharmacological actions underlying mechanisms action nuciferine, nor-nuciferine, roemerine against breast cancer. Results: Fifty-five potential targets compounds were identified. The Epidermal Growth Factor Receptor (EGFR), Mitogen-Activated Protein Kinase 8 (MAPK8), Janus 2 (JAK2), Inhibitor Nuclear Kappa B Subunit Beta (IKBKB), C Epsilon (PRKCE) identified top five Molecular demonstrated that these could bind spontaneously screened 4 targeted proteins. Conclusion: present study demonstrates have effects via multi-target multi-pathway manner.

Language: Английский

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Knockdown of a Specific Circular Non-Coding RNA Significantly Suppresses Osteosarcoma Progression

Engineering, Journal Year: 2022, Volume and Issue: 21, P. 188 - 194

Published: Jan. 4, 2022

Osteosarcoma (OS) is a malignant mesenchymal tissue tumor known to occur in children and adolescents, pulmonary metastasis often leads death these patients. The mechanism underlying OS progression remains unclear. Therefore, identifying new therapeutic targets treatment modalities for urgently needed. Abnormally expressed non-coding circular RNAs (circRNAs) are crucial the occurrence development of OS. purpose this study was explore expression role novel circRNA circ_000203 elucidate mechanism. demonstrated highly cell lines tissues, knockdown significantly inhibited vitro vivo. Furthermore, we found that sponge miR-26b-5p, an upstream regulator bone morphogenetic protein receptor 2 (BMPR2). Thus, overexpression BMPR2 could reduce inhibitory effect on progression. This indicates suppresses through microRNA (miRNA)-mediated downregulation. Our findings provide important insights understanding

Language: Английский

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circUSP34 accelerates osteosarcoma malignant progression by sponging miR‐16‐5p

Cancer Science, Journal Year: 2021, Volume and Issue: 113(1), P. 120 - 131

Published: Sept. 30, 2021

Osteosarcoma (OS) is a primary and highly malignant mesenchymal tissue tumor. The specific pathological mechanism underlying disease initiation or progression remains unclear. Circular RNAs (circRNAs) are type of covalently circular RNA with head-to-tail junction site. In this study, we aimed to investigate the sponging between circRNAs microRNAs (miRNAs) in OS. Based on inhibited effect miR-16-5p reported OS, circUSP34 was analyzed as sponge via Starbase. We found that promoted proliferation, migration, invasion OS vitro vivo. increased but decreased by qRT-PCR. Function assays showed malignancy cells, including invasion, after knocking out circUSP34. Western blotting results expression level vimentin Ki-67 decreased. Similarly, mimic compromised cells. FISH assay indicated were colocalized cytoplasm. verified dual-luciferase reporter assay, immunoprecipitation (RIP), pull down assays. Interestingly, inhibitor partly reversed inhibitory sh-circUSP34 Further, mice tumors for IHC vimentin, N-cadherin, protein decreased, E-cadherin increased. Collectively, malignancy, miR-16-5p. It can serve potential therapeutic target biomarker.

Language: Английский

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Network propagation-based prioritization of long tail genes in 17 cancer types

Genome biology, Journal Year: 2021, Volume and Issue: 22(1)

Published: Oct. 7, 2021

The diversity of genomic alterations in cancer poses challenges to fully understanding the etiologies disease. Recent interest infrequent mutations, genes that reside "long tail" mutational distribution, uncovered new with significant implications development. study cancer-relevant often requires integrative approaches pooling together multiple types biological data. Network propagation methods demonstrate high efficacy achieving this integration. Yet, majority these focus their assessment on detecting known or identifying altered subnetworks. In paper, we introduce a network approach entirely focuses prioritizing long tail potential functional impact

Language: Английский

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